Human embryonic stem cell-derived hematoendothelial progenitors engraft chicken embryos.
OBJECTIVE
To investigate whether human embryonic stem cells (hESC) committed in culture into hematopoietic/endothelial cell progenitors can be further developed into mature blood and vascular cells following transplantation into chicken embryos.


METHODS
The yolk sac of 42- to 44-hour chicken embryos received yolk sac injections of unfractionated human embryoid body (hEB) cells, CD34-positive hEB cells, or CD34+CD45+ granulocyte colony-stimulating factor-mobilized human peripheral blood hematopoietic stem-progenitor cells. Human cells in the host were detected by flow cytometry and immunohistochemistry.


RESULTS
All injected cell populations engrafted chicken hematopoietic organs, as assessed by detection of CD45+ cells in the spleen, bursa of Fabricius, and thymus. CD34+ day -10 hEB cells showed the highest efficiency for producing human CD45+ cells in the hosts and yielded human glycophorin A+ erythroid, CD13+ myeloid, and CD19+ lymphoid cells in the spleen and bursa of Fabricius. Spleen cells from chimeric embryos also contained human colony-forming units-granulocyte macrophage, as assessed in methylcellulose colony-forming assays. Human endothelial cells expressing vascular endothelial-cadherin, von Willebrand factor, CD31, and the receptor for the Ulex europaeus lectin were also observed in the yolk sac vasculature following injection of either unfractionated or CD34+ day -10 hEB cells.


CONCLUSIONS
Primitive angiohematopoietic stem cells (total and CD34+ day -10 hEB cells) as well as adult hematopoietic stem cells could home to intraembryonic blood-forming organs following injection into the yolk sac. These observations demonstrate the utility of the avian embryo as a convenient and reliable host to model the angiohematopoietic development of human embryonic, or other early stem cells.
Park
Tea Soon
TS
Stem Cell Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15213, USA.
Zambidis
Elias T
ET
Lucitti
Jennifer L
JL
Logar
Alison
A
Keller
Bradley B
BB
Péault
Bruno
B
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002460:Cell Line; D002642:Chick Embryo; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006085:Graft Survival / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
D000943:Antigens, Differentiation